|Ahead of print publication
Therapeutic results of Denver percutaneous peritoneovenous shunt in cancer patients with malignant ascites
Hiroshi Tamagawa1, Toru Aoyama2, Hirohide Inoue1, Hirohito Fujikawa1, Sho Sawazaki2, Masakatsu Numata2, Tsutomu Sato2, Takashi Oshima2, Norio Yukawa2, Manabu Morimoto3, Makoto Ueno3, Yashushi Rino2, Munetaka Masuda2
1 Department of Surgery, Kamishirane Hospital, Yokohama, Japan
2 Department of Surgery, Yokohama City University, Yokohama, Japan
3 Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan
Department of Surgery, Kamishirane Hospital, 2-65-1 Kamishirane, Asahi, Yokohama 241-0002
Source of Support: None, Conflict of Interest: None
Background: Intractable ascites secondary to malignant disease deteriorates patients' quality of life. The purpose of this study was to evaluate the safety and efficacy of percutaneous peritoneovenous (Denver) shunt in treating intractable malignant ascites in cancer patients.
Materials and Methods: Thirty-five patients who had undergone Denver peritoneovenous shunt for the treatment of ascites associated with malignant tumor from October 2014 to 2017 were retrospectively analyzed. The demographic characteristics, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analyses were performed.
Results: The sites of primary tumor were pancreatic cancer in 19 patients, bile duct cancer in 8, gallbladder cancer in 5, breast cancer in 2, and peritoneal malignant mesothelioma in 1. Palliation of abdominal distention was achieved in 29 patients (82.9%). Postoperative complications of Grade 2 or higher were seen in 11 patients (31.4%), and Grade 5 complications were observed in three patients (8.6%). Patients with a high American Society of Anesthesiologists (ASA) grade and high ascites drainage volume had a significantly higher incidence of postoperative complications than a low ASA grade and low ascites drainage volume, and a multivariate logistic analysis showed that the intraoperative ascites drainage volume was an independent risk factor for all complications.
Conclusions: The Denver shunt for malignant ascites is useful for improving patients' quality of life if the indications are selected properly. Drainage of intraoperative ascites was a risk factor for postoperative complications after the Denver shunt technique in cancer patients with malignant ascites. Further experience and discussion are necessary to establish the patient selection criteria.
Keywords: Cancer patients, Denver shunt, malignant ascites
|How to cite this URL:|
Tamagawa H, Aoyama T, Inoue H, Fujikawa H, Sawazaki S, Numata M, Sato T, Oshima T, Yukawa N, Morimoto M, Ueno M, Rino Y, Masuda M. Therapeutic results of Denver percutaneous peritoneovenous shunt in cancer patients with malignant ascites. J Can Res Ther [Epub ahead of print] [cited 2020 Mar 31]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=264703
| > Introduction|| |
Ascites is a frequent cause of distress in patients with advanced malignant neoplasms, and unfortunately, it usually heralds the terminal phase of their illness. The treatment of malignant ascites is primarily the treatment of an underlying neoplastic process. However, the management of the fluid accumulation per se can substantially improve the comfort, physical activity, and quality of life of these patients. Certainly, traditional methods of treatment, such as sodium and fluid restriction, diuretics, and instillation of chemotherapeutic agents, are often unsuccessful and repeated paracentesis becomes necessary. These procedures involve considerable patient discomfort and loss of precious proteins and electrolytes that patients can ill afford.
Leveen et al. introduced a peritoneovenous shunt that he designed to transmit ascites from the peritoneal cavity back into the central venous circulation in 1974. The shunt, which was surgically placed, had a one-way valve to prevent backflow of venous blood. The most recent development in this field is a modified version of a shunt developed for the treatment of hydrocephalus, commonly known as the Denver Shunt, and our hospital placed the most Denver shunts in Japan during the period of 2014–2016.
Peritoneovenous shunt placement has been primarily used for symptomatic relief in patients with intractable malignant ascites, and the procedure has been described as effective and safe in this population. However, while several reports have described its efficacy in ascites due to liver disease, it has infrequently been used for the management of malignant ascites.,,
In this article, we describe our experience with a peritoneovenous shunt for malignant ascites.
| > Materials and Methods|| |
This retrospective study was conducted under an exemption from the Institutional Review Board. We analyzed 35 patients who underwent the placement of a Denver shunt (Mihama Medical, Inc., Tokyo, Japan) for the treatment of refractory ascites caused by peritoneal dissemination of a malignant tumor at our institute from April 2014 to October 2017. Patients with hepatocellular carcinoma were excluded from this study. The shunt was detained using the previously reported method. The internal jugular vein detected by ultrasound, and the right side was accessed when possible. The procedure was performed under general and monitored anesthesia care. Patients received a first-generation cephalosporin antibiotic intravenously within 1 h of the procedure as prophylaxis. Before shunt placement, approximately 1000–2000 ml of ascites was drained, leaving only a small amount of ascites with which to prime the shunt. All patients were admitted and observed the signs of disseminated intravascular coagulation (DIC) and another postoperative complication. The patients were instructed to pump the shunt 20 times, twice a day (once in the morning and once before bed) while in the supine position. Effective palliation was defined as improvement in at least one of the patient's symptoms and no further need for paracentesis. All patients who received a Denver shunt had progressive disease despite previous treatments, including chemotherapy, and some patients received additional anticancer treatment.
The following data were collected and analyzed retrospectively: the patient demographic and clinicopathological features, including age, gender, site of primary tumor, body mass index (BMI), American Society of Anesthesiologists (ASA) grade, and performance status (PS); the presence or absence of administration of diuretics, the presence or absence of narcotic analgesics, history of treatment, presence or absence of paracentesis, and comorbidity; and postoperative outcomes, including operative mortality and postoperative complications. Postoperative complications were classified according to the Clavien–Dindo classification. Severe complications were defined as those of Grade III or above, and operative mortality was defined as death within 30 days of the operation.
The relationship between postoperative complications and potential explanatory variables, including the age, gender, tumor size, histological type, depth of invasion, lymph node metastasis, and location, was evaluated using the Chi-square test. A logistic regression analysis was used for the multivariate analyses. The postoperative survival rate from the day of shunt placement was analyzed using the Kaplan–Meier method, and any differences in the survival rates were assessed with the log-rank test. Differences were considered significant when P < 0.05. Statistical analyses were performed using the Dr. SPSS II software program, version 11.0.1J for Windows (SPSS, Inc., Chicago, IL, USA).
| > Results|| |
From April 2014 to October 2017, 35 patients met our inclusion criteria and were included in the analysis. The patient demographic and clinical characteristics are summarized in [Table 1]. The median age was 61 years (range: 35–79 years), and pancreatic cancer (54.3%) was the most common primary tumor. Twenty-three patients (65.8%) with a PS of ≥2 and eight patients (22.9%) with an ASA grade of 3 were deemed to have a poor general condition. Diuretics were introduced in 31 patients (88.6%), and 11 (31.4%) were using narcotics to relieve their abdominal symptoms. Ascites puncture was performed before surgery in 17 cases (48.6%). An abdominal bloating sensation was reported in all cases, and 25 cases (71.4%) of anorexia were noted.
Short-term postoperative outcomes
Abdominal fullness was improved in 28 of 35 patients (80%). Improvement in the abdominal circumference was found in 27 patients (preoperative average 90.3 ± 6.3 cm, postoperative average 85.3 ± 8.3 cm). Anorexia was improved in 15 of 25 patients (60%). The postoperative hospital stay was a median of 4 days (range: 0–24 days).
Total postoperative complications occurred in 11 patients (31.4%), and severe complications of Grade ≥III in the Clavien–Dindo classification occurred in 4 patients (11.4%). The details of the postoperative complications according to the Clavien–Dindo classification are summarized in [Table 2]. Five patients (14.3%) developed DIC, and four were treated with DIC such as blood transfusion. Patients with ASA Grade 3 had a significantly higher incidence of total complications than those with a lower grade [18.5% vs. 75.0%, P = 0.0003; [Table 3]. The average value of each factor and the results of the examination of postoperative complications are shown in [Table 4]. The volume of intraoperative ascites drainage (75.0% vs. 25.8%, P = 0.0003), hemoglobin reduction rate (75.0% vs. 25.8%, P = 0.001), and thrombocytopenia rate (75.0% vs. 25.8%, P = 0.038) were significantly higher in cases with postoperative complications than in those without such complications. The multivariate logistic analysis showed that the volume of intraoperative ascites drainage was an independent risk factor for all complications [Table 5].
|Table 2: Details of postoperative complications according to the Clavien-Dindo classification|
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|Table 3: Multivariate Logistic Regression Analysis of Factors Associated with Postoperative Complications|
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|Table 5: Multivariate Logistic Regression Analysis of Factors Associated with Postoperative Complications|
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Long-term postoperative outcomes
Postoperative shunt obstruction was confirmed in eight cases. Two of them were reopened by urokinase shunt administration, while one case received a replacement with another shunt. The overall survival after surgery is shown in [Figure 1] (median follow-up was 13 months [range: 1.5–17 months]). The presence of postoperative complications was a risk factor for these patients.
| > Discussion|| |
Central venous thrombosis and pulmonary embolism are severe complications that have been reported in association with the use of peritoneovenous shunts. In the present study, two patients died the day after the operation. Biagini et al. reported that the most serious complication was central venous thrombosis, occurring in 11 (23.4%) of 47 procedures, including one case of nonfatal and two cases of fatal pulmonary emboli. After placement of peritoneal-venous shunts, conspicuous coagulopathy abnormalities, such as fibrinogen and platelet reduction, often temporarily occur. Suggested cases of thrombosis include a decreased blood flow velocity due to right heart failure, the disturbance of the endocardium by the tip of the catheter, the effect of preclotting active substances, and the influx of endotoxin in the ascites.,
DIC is also a serious obstacle following this surgical strategy. The incidence of clinical DIC after the placement of peritoneovenous shunts was reported to range from 2% to 5.3%., Lund and Moritz  reported that the incidence of clinical or overt DIC was as high as 35%, predominately in early reports. In the present study, five patients (14.3%) developed clinical DIC, including one case of perioperative death. The relationship between the shunt and DIC is unclear; however, it may be that peritoneovenous shunts alter the coagulation system by the continuous venous infusion of ascites, thus causing DIC. One of the proposed mechanisms underlying the development of DIC is the rapid introduction of ascitic fluid containing high levels of fibrin-rich procoagulants, including endotoxin, thromboplastin-activated clotting factors, and plasminogen activator, into the central venous system. These procoagulant factors ultimately activate the coagulation pathway. The presence of preoperative coagulation abnormalities and hyperbilirubinemia has been suggested as risk factors for the onset of DIC;,, however, in the present study, we noted no correlation between these risk factors and the occurrence of DIC.
In this study, the volume of intraoperative ascites drainage was found to be an independent risk factor for all complications. Yarmohammadi et al. suggested that the risk of DIC could be reduced by draining the ascites to completion at the time of shunt placement and replacing the ascites with 4 L of normal saline to avoid putting into circulation a large volume of potentially DIC-inducing substances that might be present in the ascites. While Lerner et al. reported that the reinfusion of ascites is useful for predicting DIC, others have reported conflicting findings, and when the reinfusion of ascites was performed in three out of the eight patients with DIC, none developed DIC after reinfusion of ascites.
Postoperative shunt obstruction was confirmed in eight cases in this study. Urokinase thrombolytic therapy was used to lyse the thrombosed Denver peritoneovenous shunts in three cases, and reopening was possible in two cases. Lerner et al. suggested that thrombolytic therapy might be a viable alternative to immediate surgical revision in patients with failed Denver shunts.
| > Conclusions|| |
The Denver shunt is effective and provides excellent palliation as a treatment modality for malignant ascites. Drainage of intraoperative ascites was a risk factor for postoperative complications after the Denver shunt technique in cancer patients with malignant ascites. Further experience and discussion are necessary to establish the patient selection criteria.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Garrison RN, Kaelin LD, Galloway RH, Heuser LS. Malignant ascites. Clinical and experimental observations. Ann Surg 1986;203:644-51.
Leveen HH, Christoudias G, Ip M, Luft R, Falk G, Grosberg S. Peritoneo-venous shunting for ascites. Ann Surg 1974;180:580-91.
White MA, Agle SC, Padia RK, Zervos EE. Denver peritoneovenous shunts for the management of malignant ascites: A review of the literature in the post LeVeen Era. Am Surg 2011;77:1070-5.
Straus AK, Roseman DL, Shapiro TM. Peritoneovenous shunting in the management of malignant ascites. Arch Surg 1979;114:489-91.
Qazi R, Savlov ED. Peritoneovenous shunt for palliation of malignant ascites. Cancer 1982;49:600-2.
Lokich J, Reinhold R, Silverman M, Tullis J. Complications of peritoneovenous shunt for malignant ascites. Cancer Treat Rep 1980;64:305-9.
Martin L. Percutaneous placement and management of peritoneovenous shunts. Semin Intervent Radiol 2012;29:129-34.
Biagini JR, Belghiti J, Fekete F. Prevention of coagulopathy after placement of peritoneovenous shunt with replacement of ascitic fluid by normal saline solution. Surg Gynecol Obstet 1986;163:315-8.
Goldfarb AN. Cardiopulmonary thrombosis complicating peritoneovenous shunting: A case report and review of the literature. Am J Cardiovasc Pathol 1988;2:259-62.
Smith EM, Jayson GC. The current and future management of malignant ascites. Clin Oncol (R Coll Radiol) 2003;15:59-72.
Sugawara S, Sone M, Arai Y, Sakamoto N, Aramaki T, Sato Y, et al.
Radiological insertion of denver peritoneovenous shunts for malignant refractory ascites: A retrospective multicenter study (JIVROSG-0809). Cardiovasc Intervent Radiol 2011;34:980-8.
Lund RH, Moritz MW. Complications of denver peritoneovenous shunting. Arch Surg 1982;117:924-8.
Ragni MV, Lewis JH, Spero JA. Ascites-induced leVeen shunt coagulopathy. Ann Surg 1983;198:91-5.
Adam RA, Adam YG. Malignant ascites: Past, present, and future. J Am Coll Surg 2004;198:999-1011.
Yarmohammadi H, Brody LA, Erinjeri JP, Covey AM, Boas FE, Ziv E, et al.
Therapeutic application of percutaneous peritoneovenous (Denver) shunt in treating chylous ascites in cancer patients. J Vasc Interv Radiol 2016;27:665-73.
Lerner RG, Nelson JC, Corines P, del Guercio LR. Disseminated intravascular coagulation. Complication of leVeen peritoneovenous shunts. JAMA 1978;240:2064-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]